Search

The warpage of the package substrate mainly originates from the material property and size variations of individual components, especially when multiple components are involved. To maintain the substrate warpage within acceptable limits, it’s crucial to fine-tune component parameters carefully, choosing appropriate materials and processing conditions. The current study investigates the factors influencing substrate warpage and explores the methods to mitigate it with the assistance of finite element analysis. Glass fiber reinforced epoxy-based substrates were prepared under different curing temperatures, and characterized by thermo-mechanical analysis and mechanical testing. A finite element simulation model of the bare carrier board was developed using ABAQUS software. The results show that the curing temperature impacts the coefficient of thermal expansion (CTE), strength and modulus of the substrate. The differences in CTE and dimensional parameters among the component materials strongly influence substrate warpage. While the curing conditions affect bare carrier board warpage to some extent, the type and thickness of solder mask have more significant effects and warpage can be mitigated by properly choosing and applying solder masks. [ABSTRACT FROM AUTHOR]

Brain-inspired neuromorphic computing has emerged as a promising solution to overcome the energy and speed limitations of conventional von Neumann architectures. In this context, in-memory computing utilizing memristors has gained attention as a key technology, harnessing their non-volatile characteristics to replicate synaptic behavior akin to the human brain. However, challenges arise from non-linearities, asymmetries, and device variations in memristive devices during synaptic weight updates, leading to inaccurate weight adjustments and diminished recognition accuracy. Moreover, the repetitive weight updates pose endurance challenges for these devices, adversely affecting latency and energy consumption. To address these issues, we propose a Siamese network learning approach to optimize the training of multi-level memristor neural networks. During neural inference, forward propagation takes place within the memristor neural network, enabling error and noise detection in the memristive devices and hardware circuits. Simultaneously, high-precision gradient computation occurs on the software side, initially updating the floating-point weights within the Siamese network with gradients. Subsequently, weight quantization is performed, and the memristor conductance values requiring updates are modified using a sparse update strategy. Additionally, we introduce gradient accumulation and weight quantization error compensation to further enhance network performance. The experimental results of MNIST data recognition, whether based on a MLP or a CNN model, demonstrate the rapid convergence of our network model. Moreover, our method successfully eliminates over 98% of weight updates for memristor conductance weights within a single epoch. This substantial reduction in weight updates leads to a significant decrease in energy consumption and time delay by more than 98% when compared to the basic closed-loop update method. Consequently, this approach effectively addresses the durability requirements of memristive devices. [ABSTRACT FROM AUTHOR]

Natalisin (NTL) is a conserved neuropeptide, only present in insects, that has been reported to regulate their sexual activity. In this study, we investigated the involvement of NTL in the reproductive behaviors of a major invasive pest, Spodoptera frugiperda. We identified NTL precursor-encoded transcripts, and evaluated their transcript levels in different stages and tissues of S. frugiperda. The results showed that the NTL transcript level was expressed in both male and female pupae and both male and female adults in the later stage. It was highly expressed in male pupae, 3-day-old male and female adults, and 5-day-old male adults. In different tissues, the expression level is higher in the male and female adult brain and male testis. Immunohistochemical staining of the brain of S. frugiperda female and male adults revealed that three pairs of brain neurons of S. frugiperda adults of both sexes secreted and expressed NTL. To study the role of NTL in reproductive behaviors, NTL was silenced in S. frugiperda male and female adults by RNA interference (RNAi) technology, the results showed that silencing NTL could significantly affect the sexual activity behavior of the adults, reducing the calling rate of females, the courtship rate of males, and the mating rate. In summary, this study emphasizes the important role of NTL in regulating the mating behavior and sexual activity of S. frugiperda in both male and female adults, potentially laying a foundation to employ NTL as a new insect-specific target to control populations of pest insects. [ABSTRACT FROM AUTHOR]

The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis BLa80, as an adjunct treatment for diarrhea in children with a randomized, double-blinded, placebo-controlled study design. Eligible diarrheal children, aged 0–3 years without the need for antibiotic treatment based on clinical diagnosis when recruited, were randomized into the intervention group (IG, n = 58, with probiotic) or the control group (CG, n = 53, placebo). The primary assessment was the duration of diarrhea. Fecal samples were collected for biochemical index measurement, analysis of gut microbiome composition, and prediction of gene family abundances. The total duration of diarrhea in the IG (122.6 ± 13.1 h) was significantly shorter than in the CG (148.4 ± 17.6 h, p < 0.001). More children in the IG showed improvements in diarrhea compared to the CG, both in intention-to-treat analysis (81.7% vs. 40.0%, p < 0.001) and per protocol analysis (84.4% vs 45.3%, p < 0.001). Cathelicidin level in the IG was significantly higher than that in the CG after the intervention (4415.00 ± 1036.93 pg/g vs. 3679.49 ± 871.18 pg/g, p = 0.0175). The intervention led to an increased abundance of Bifidobacterium breve and Collinsella aerofaciens species, higher alpha-diversity (p < 0.05), and enrichment of functional genes in the gut microbiota related to immunity regulation. Administration of BLa80 at a dose of 5 × 109 CFU/day resulted in a shorter duration of diarrhea and alterations in gut microbiome composition and gene functions. [ABSTRACT FROM AUTHOR]

The giant panda (Ailuropoda melanoleuca), as an endemic species of China, is also a flagship species of wildlife Conservation. However, the accuracy of individual identification of giant pandas is typically problematic due to the high error rate of microsatellite typing methods. In this study, a panel of 61 SNP makers was developed for individual identification. Of these, 55 polymorphic SNP markers were successfully genotyped. The observed heterozygosity (Ho), expected heterozygosity (He) and polymorphic information content (PIC) ranged from 0.056 to 0.611 (mean 0.352), 0.131–0.509 (mean 0.389) and 0.099–0.389(mean 0.305), respectively. No SNPs significantly deviated from Hardy–Weinberg equilibrium (P < 0.05). Our study provides a framework for improving the accuracy of individual identification of giant pandas, especially for poor quality samples collected from the wild. [ABSTRACT FROM AUTHOR]

The diagnostic accuracy of clinically significant prostate cancer (csPCa) of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) is limited by subjectivity in result interpretation and the false positive results from certain similar anatomic structures. We aimed to establish a new model combining quantitative contrast-enhanced ultrasound, PI-RADSv2, clinical parameters to optimize the PI-RADSv2-based model. The analysis was conducted based on a data set of 151 patients from 2019 to 2022, multiple regression analysis showed that prostate specific antigen density, age, PI-RADSv2, quantitative parameters (rush time, wash-out area under the curve) were independent predictors. Based on these predictors, we established a new predictive model, the AUCs of the model were 0.910 and 0.879 in training and validation cohort, which were higher than those of PI-RADSv2-based model (0.865 and 0.821 in training and validation cohort). Net Reclassification Index analysis indicated that the new predictive model improved the classification of patients. Decision curve analysis showed that in most risk probabilities, the new predictive model improved the clinical utility of PI-RADSv2-based model. Generally, this new predictive model showed that quantitative parameters from contrast enhanced ultrasound could help to improve the diagnostic performance of PI-RADSv2 based model in detecting csPCa. [ABSTRACT FROM AUTHOR]

Background: This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency syndrome. Methods: Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome sequencing. We analyzed the patients' convulsions and treatment with antiepileptic drugs. The patients were followed up at different time periods after ketogenic diet therapies. Results: Six patients with SLC2A1 mutations were included in this study. The patients had seizures of different types and frequencies, and they took antiepileptic drugs to relieve their symptoms. They were then treated with a ketogenic diet for at least four months. We analyzed epilepsy control rates at 1, 2, 3, 6, and 12 months after ketogenic diet treatment. All patients were seizure-free within a month of receiving the diet therapy. All patients were followed up for six months, three were followed up for 12 months after the treatment, and there was no recurrence of epilepsy during this period. After antiepileptic drug withdrawal, none of the patients experienced seizure relapse when receiving ketogenic diet treatment alone. No severe adverse events occurred during the therapy. Conclusions: Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 mutations. Therefore, patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible. [ABSTRACT FROM AUTHOR]

Purpose: The study aims to investigate whether including the inflammation-related parameters would enhance the accuracy of a nomogram for local control (LC) prediction in lung cancer patients undergoing stereotactic body radiation therapy (SBRT). Methods: 158 primary or metastatic lung cancer patients treated with SBRT were retrospectively analyzed. The clinical, dosimetric and inflammation-related parameters were collected for the Cox regression analysis. The ACPB model was constructed by employing the clinical and dosimetric factors. And the ACPBLN model was established by adding the inflammation-related factors to the ACPB model. The two models were compared in terms of ROC, Akaike Information Criterion (AIC), C-index, time-dependent AUC, continuous net reclassification index (NRI), integrated discrimination improvement (IDI), calibration plots and decision curve analysis (DCA). Results: Multivariate Cox regression analysis revealed that six prognostic factors were independently associated with LC, including age, clinical stage, planning target volume (PTV) volume, BED of the prescribed dose (BEDPD), the lymphocyte count and neutrocyte count. The ACPBLN model performed better in AIC, bootstrap-corrected C-index, time-dependent AUC, NRI and IDI than the ACPB model. The calibration plots showed good consistency between the probabilities and observed values in the two models. The DCA curves showed that the ACPBLN nomogram had higher overall net benefit than the ACPB model across a majority of threshold probabilities. Conclusion: The inflammation-related parameters were associated with LC for lung cancer patients treated with SBRT. The inclusion of the inflammation-related parameters improved the predictive performance of the nomogram for LC prediction. [ABSTRACT FROM AUTHOR]

We develop an invariant theory of quasi-split ı quantum groups U n ı of type AIII on a tensor space associated to ı Howe dualities. The first and second fundamental theorems for U n ı -invariants are derived. [ABSTRACT FROM AUTHOR]

The increasing threat of ocean warming has led to the more frequent endangerment of coral reefs, including the heat-tolerant Pavona decussata. To shed light on the molecular mechanisms involved in the response of coral to ocean warming, we investigated the gene expression profiles of P. decussata after natural thermal stress. Using PacBio Sequel II sequencing technology, we obtained relatively complete transcriptome data for P. decussata and then analyzed its gene expression quantitatively with Illumina RNA-seq technology. We acquired information on gene function, structure, and expression profile from coral host and zooxanthellae. Analysis of Illumina sequencing data revealed that unbleached coral host might rely on the active utilization of amino acids to maintain a stable living condition based on the tricarboxylic acid cycle under high temperature stress, and that zooxanthellae might benefit from ammonium produced by coral host. Moreover, the downregulation of unbleached coral host gene expression in innate immune pathways centered on the transcription factors that heat shock factor and nuclear factor (NF)-κB, as well as the tyrosine kinase pathway, might be crucial for maintaining the equilibrium of the zooxanthellae under thermal stress. Thus, the differences in these molecular mechanisms could determine, to some extent, whether coral host can maintain a symbiotic relationship with algae under heat stress. This study elucidated the molecular mechanisms underlying differences in thermal tolerance within P. decussata species and supported further theoretical basis in coral molecular biology and ecological conservation, which enhance our comprehension of coral responses to future climate change. [ABSTRACT FROM AUTHOR]

Cancer cells are often addicted to serine synthesis to support growth. How serine synthesis is regulated in cancer is not well understood. We recently demonstrated protein arginine methyltransferase 1 (PRMT1) is upregulated in hepatocellular carcinoma (HCC) to methylate and activate phosphoglycerate dehydrogenase (PHGDH), thereby promoting serine synthesis. However, the mechanisms underlying PRMT1 upregulation and regulation of PRMT1-PHGDH axis remain unclear. Here, we show the E3 ubiquitin ligase F-box-only protein 7 (FBXO7) inhibits serine synthesis in HCC by binding PRMT1, inducing lysine 37 ubiquitination, and promoting proteosomal degradation of PRMT1. FBXO7-mediated PRMT1 downregulation cripples PHGDH arginine methylation and activation, resulting in impaired serine synthesis, accumulation of reactive oxygen species (ROS), and inhibition of HCC cell growth. Notably, FBXO7 is significantly downregulated in human HCC tissues, and inversely associated with PRMT1 protein and PHGDH methylation level. Overall, our study provides mechanistic insights into the regulation of cancer serine synthesis by FBXO7-PRMT1-PHGDH axis, and will facilitate the development of serine-targeting strategies for cancer therapy.How serine synthesis is regulated in cancer remains to be further explored. Here the authors identify FBXO7, an E3 ubiquitin ligase, inhibits serine synthesis in hepatocellular carcinoma by promoting ubiquitination and degradation of PRMT1 methyltransferase. [ABSTRACT FROM AUTHOR]

Marine mussels can adhere to various surfaces in a liquid environment by utilizing pedicle filaments, with the adhesive properties primarily attributed to the structure of catechol, the main component of the filament. To overcome the challenges associated with the complex preparation process, high cost, and potential biological rejection of naturally extracted or recombinantly expressed mussel proteins, researchers drew inspiration from mussels and utilized an oxidative crosslinking approach to prepare adhesive hydrogel materials. However, the hydrogels prepared using this method exhibited inferior mechanical properties and low viscosity. To address these limitations, in this study, a kind of mussel-inspired dual-crosslinked hydrogel was prepared by dual cross-linking with hydroxypropyl chitosan (HPCS) and hyaluronic acid (HA), based on catechol, an adhesion component in marine mussel pedicle filaments. Comparative analysis revealed that the mussel-inspired dual-crosslinked hydrogel exhibited significantly higher adhesion strength (up to 33.96 kPa) and improved mechanical properties (energy storage modulus ranging from 489 to 1032 Pa) compared to the mussel-inspired oxidatively cross-linked hydrogel. In addition, the mussel-inspired dual-crosslinked hydrogel demonstrated favorable swelling (up to 136.54 ± 0.22%), degradation, sustained-release, bacteriostatic and biocompatible properties. These findings suggest a promising potential for future applications in the field of biomedical materials. [ABSTRACT FROM AUTHOR]

Narirutin (Nar) is a flavonoid that is abundantly present in citrus fruits and has attracted considerable attention because of its diverse pharmacological activities and low toxicity. Here, we evaluated the preventive effects of Nar in middle cerebral artery occlusion/reperfusion (MCAO/R)-injured mice and oxygen–glucose deprivation/reperfusion (OGD/R)-injured bEnd.3 cells. Pretreatment with Nar (150 mg/kg) for 7 days effectively reduced infarct volume, improved neurological deficits, and significantly inhibited neuronal death in the hippocampus and cortex in MCAO/R-injured mice. Moreover, anti-apoptotic effects of Nar (50 µM) were observed in OGD/R-injured bEnd.3 cells. In addition, Nar pre-administration regulated blood-brain barrier function by increasing tight junction-related protein expression after MCAO/R and OGD/R injury. Nar also inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation by reducing the expression of thioredoxin-interacting protein (TXNIP) in vivo and in vitro. Taken together, these results provide new evidence for the use of Nar in the prevention and treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

A non-invasive, fast, and reliable method for sex identification of the giant panda (Ailuropoda melanoleuca) was developed by genotyping five SNPs located at the sex chromosome amelogenin (AMEL) paralogs. The giant panda's sex can be accurately distinguished by the homozygous or heterozygous SNP genotypes. Mass spectrometry assay and Sanger sequencing both successfully genotyped tissue and fresh fecal samples collected from known-sex giant pandas. Additionally, we simulated the conditions of wild fecal samples, which were naturally degraded for up to two weeks, and successfully genotyped these samples by mass spectrometry assay in parallel. These results suggest that this is a powerful method for sex determination in highly degraded and lower concentrated DNA samples. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to translate and culturally adapt the standardized outcomes in nephrology–hemodialysis fatigue (SONG–HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG–HD fatigue (C-SONG–HD fatigue) scale. Methods: Forward and back translations were used to translate the SONG–HD fatigue scale into Chinese. We used the C-SONG–HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test–retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. Results: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG–HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test–retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. Conclusion: The Chinese version of the SONG–HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients. [ABSTRACT FROM AUTHOR]

Purpose: Chemoresistance is a major challenge for acute lymphoblastic leukemia (ALL) treatment. Cysteine-rich protein 61 (Cyr61) plays an important role in drug resistance modulation of tumor cells, and Cyr61 levels are increased in the bone marrow of patients with ALL and contribute to ALL cell survival. However, the effect of Cyr61 on B cell acute lymphoblastic leukemia (B-ALL) cell chemosensitivity and the regulatory mechanisms underlying Cyr61 production in bone marrow remain unknown. Methods: Nalm-6 and Reh human B-ALL cell lines were used in this study. Cyr61 levels were assessed using quantitative real-time PCR (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay. The effect of Cyr61 on B-ALL cell chemosensitivity to daunorubicin (DNR) was evaluated using cell viability and flow cytometry analyses. The regulatory mechanisms of Cyr61 production in bone marrow were examined using qRT-PCR and western blot analysis. Results: Cyr61 knockdown and overexpression increased and decreased the chemosensitivity of B-ALL cells to DNR, respectively. Cyr61 attenuated chemotherapeutic drug-induced apoptosis by upregulating B cell lymphoma-2. Notably, DNR induced DNA damage response and increased Cyr61 secretion in B-ALL cells through the ataxia telangiectasia mutated (ATM)-dependent nuclear factor kappa B pathway. Conclusion: DNR induces Cyr61 production in B-ALL cells, and increased Cyr61 levels reduce the chemosensitivity of B-ALL cells. Consequently, targeting Cyr61 or related ATM signaling pathway may present a promising treatment strategy to enhance the chemosensitivity of patients with B-ALL. [ABSTRACT FROM AUTHOR]

The complexity of the tumor microenvironment (TME) is a crucial factor in lung adenocarcinoma (LUAD) progression. To gain deeper insights into molecular mechanisms of LUAD, we perform an integrative single-cell RNA sequencing (scRNA-seq) data analysis of 377,574 cells from 117 LUAD patient samples. By linking scRNA-seq data with bulk gene expression data, we identify a cluster of prognostic-related UPP1high tumor cells. These cells, primarily situated at the invasive front of tumors, display a stronger association with the immunosuppressive components in the TME. Our cytokine array analysis reveals that the upregulation of UPP1 in tumor cells leads to the increased release of various immunosuppressive cytokines, with TGF-β1 being particularly prominent. Furthermore, this UPP1 upregulation also elevates the expression of PD-L1 through the PI3K/AKT/mTOR pathway, which contributes to the suppression of CD8 + T cells. Cytometry by time-of-flight (CyTOF) analysis provides additional evidence of the role of UPP1 in shaping the immunosuppressive nature of the TME. Using patient-derived organoids (PDOs), we discover that UPP1high tumors exhibit relatively increased sensitivity to Bosutinib and Dasatinib. Collectively, our study highlights the immunosuppressive role of UPP1 in LUAD, and these findings may provide insights into the molecular features of LUAD and facilitate the development of personalized treatment strategies. Characterising the tumour microenvironment features of lung adenocarcinoma (LUAD) remains crucial. Here, the authors perform single cell RNA sequencing data analysis of 117 LUAD samples and functional assays and highlight the immunosuppressive role of UPP1high tumour cells. [ABSTRACT FROM AUTHOR]

Purpose: Hilly areas are highly susceptible to soil erosion. This study aims to discover the drivers of soil erosion, identify soil erosion–sensitive areas, and predict future soil erosion in typical hilly areas of Hubei Province, China, using combined RUSLE and LSTM models. Materials and methods: In this study, soil erosion in hilly areas of Hubei Province from 2000 to 2020 was quantitatively analyzed using the revised universal soil loss equation (RUSLE), and the soil erosion sensitivity evaluation system was constructed, a geographic detector was employed to identify the main drivers of soil erosion sensitivity, and using the long short-term memory neural network model (LSTM) to predict soil erosion in 2025. Results and discussions: The results showed that most areas were dominated by slight and moderate erosion. Slope and vegetation coverage were identified as the core elements influencing the space heterogeneity of soil erosion. Soil erosion sensitivity was mainly composed of moderate sensitivity, accounting for more than 70% of the total area. The strong and extreme sensitivity demonstrated a downward trend with the continued implementation of slope management and forest rehabilitation from slope agriculture, whereas the sensitivity was still higher in the northwest and southwest Hubei Province. Regions with severe soil erosion had high sensitivity, and the spatial distribution of the two is strongly coherent. Areas with surface relief > 300 m and vegetation cover < 30% had the highest sensitivity and should be highly valued. The percentage of moderate and higher soil erosion area in 2025 was 3.77% lower than in 2020, but severe erosion still exists in the northwest and southwest Hubei Province. Conclusions: Soil erosion sensitivity in the western part of the study area was the highest, followed by the southeast, and the overall erosion sensitivity was gradually decreasing during the studied period. In the future, soil erosion intensity will show a downward trend, whereas the deployment of soil and water conservation measures in soil erosion–sensitive areas should still be strengthened. The results are helpful for accurate soil erosion control and prediction in the hilly areas of Hubei Province, China. [ABSTRACT FROM AUTHOR]

Accurate prognostic prediction is crucial for treatment decision-making in lung papillary adenocarcinoma (LPADC). The aim of this study was to predict cancer-specific survival in LPADC using ensemble machine learning and classical Cox regression models. Moreover, models were evaluated to provide recommendations based on quantitative data for personalized treatment of LPADC. Data of patients diagnosed with LPADC (2004–2018) were extracted from the Surveillance, Epidemiology, and End Results database. The set of samples was randomly divided into the training and validation sets at a ratio of 7:3. Three ensemble models were selected, namely gradient boosting survival (GBS), random survival forest (RSF), and extra survival trees (EST). In addition, Cox proportional hazards (CoxPH) regression was used to construct the prognostic models. The Harrell's concordance index (C-index), integrated Brier score (IBS), and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the performance of the predictive models. A user-friendly web access panel was provided to easily evaluate the model for the prediction of survival and treatment recommendations. A total of 3615 patients were randomly divided into the training and validation cohorts (n = 2530 and 1085, respectively). The extra survival trees, RSF, GBS, and CoxPH models showed good discriminative ability and calibration in both the training and validation cohorts (mean of time-dependent AUC: > 0.84 and > 0.82; C-index: > 0.79 and > 0.77; IBS: < 0.16 and < 0.17, respectively). The RSF and GBS models were more consistent than the CoxPH model in predicting long-term survival. We implemented the developed models as web applications for deployment into clinical practice (accessible through https://shinyshine-820-lpaprediction-model-z3ubbu.streamlit.app/). All four prognostic models showed good discriminative ability and calibration. The RSF and GBS models exhibited the highest effectiveness among all models in predicting the long-term cancer-specific survival of patients with LPADC. This approach may facilitate the development of personalized treatment plans and prediction of prognosis for LPADC. [ABSTRACT FROM AUTHOR]

Environmental epidemiology studies require accurate estimations of exposure intensities to air pollution. The process from air pollutant emission to individual exposure is however complex and nonlinear, which poses significant modeling challenges. This study aims to develop an exposure assessment model that can strike a balance between accuracy, complexity, and usability. In this regard, neural networks offer one possible approach. This study employed a custom-designed pruned feed-forward neural network (pruned-FNN) approach to calculate the air pollution exposure index based on emission time and rates, terrain factors, meteorological conditions, and proximity measurements. The model's performance was evaluated by cross-validating the estimated exposure indexes with ground-based monitoring records. The pruned FNN can predict pollution exposure indexes (PEIs) that are highly and stably correlated with the monitored air pollutant concentrations (Spearman's rank correlation coefficients for tenfold cross-validation (mean ± standard deviation: 0.906 ± 0.028) and for random cross-validation (0.913 ± 0.024)). The predicted values are also close to the ground truth in most cases (95.5% of the predicted PEIs have relative errors smaller than 10%) when the training datasets are sufficiently large and well-covered. The pruned-FNN method can make accurate exposure estimations using a flexible number of variables and less extensive data in a less money/time-consuming manner. Compared to other exposure assessment models, the pruned FNN is an appropriate and effective approach for exposure assessment that covers a large geographic area over a long period of time. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) is the driver gene with the highest frequency of mutations in lung adenocarcinoma and can guide the development of targeted therapies. The detection of routine gene mutations must be performed after the preparation of paraffin samples in a standard polymerase chain reaction (PCR) laboratory, which is time-consuming. The Idylla™ EGFR fully automatic PCR system for rapid detection requires no special detection environment and completes the process in only 2.5 h. It has been applied to tissues embedded in paraffin. Methods: The Idylla™ EGFR automated PCR system was used to detect EGFR gene mutations in intraoperative frozen fresh tissues and paraffin-embedded tissues from 47 enrolled patients with lung adenocarcinoma. The gold standard amplification refractory mutation system (ARMS) method for gene mutation detection was used for verification, and the concordance between the three detection results was compared, to investigate the feasibility of detecting rapid gene mutations in intraoperative frozen samples. Results: The EGFR mutation rate in 47 fresh samples of lung adenocarcinoma was 61.7% (29/47), which is consistent with the mutation level of lung adenocarcinoma in the Asian population (38.8–64.0%). The concordance rate between the Idylla™ frozen tissues and paraffin-embedded tissues was 91.4% (43/47) when compared to the ARMS method, while the coincidence rate between the two methods was 93.6% (44/47). The three methods had a total consistency rate of 89.4% (42/47). Conclusions: The Idylla™ EGFR fully automatic PCR system directly detects EGFR mutations in fresh tissues. The operation is simple, the detection time is short, and the accuracy is high. The detection time is reduced to 1/4–1/3 of the original time while meeting clinical standards for detecting the gene status of patients, thus saving crucial time for individualized and accurate treatment of patients. The method has promising clinical application prospects. [ABSTRACT FROM AUTHOR]

Infants with low birth weight (LBW) are more likely to have health problems than normal weight infants. In studies examining the associations between particulate matter (PM) exposures and LBW, there is a tendency to focus on PM2.5 as a whole. However, insufficient information is available regarding the effects of different components of PM2.5 on birth weight. This study identified the associations between maternal exposure to 10 metal components of PM2.5 and LBW in offspring based on small area (divided by population size) level data in New Mexico, USA, from 2012 to 2016. This study used a pruned feed-forward neural network (pruned-FNN) approach to estimate the annual average exposure index to each metal component in each small area. The linear regression model was employed to examine the association between maternal PM2.5 metal exposures and LBW rate in small areas, adjusting for the female percentage and race/ethnicity compositions, marriage status, and educational level in the population. An interquartile range increase in maternal exposure to mercury and chromium of PM2.5 increased LBW rate by 0.43% (95% confidence interval (CI): 0.18–0.68%) and 0.63% (95% CI: 0.15–1.12%), respectively. These findings suggest that maternal exposure to metal components of air pollutants may increase the risk of LBW in offspring. With no similar studies in New Mexico, this study also posed great importance because of a higher LBW rate in New Mexico than the national average. These findings provide critical information to inform further epidemiological, biological, and toxicological studies. [ABSTRACT FROM AUTHOR]

Contagious disease pandemics, such as COVID-19, can cause hospitals around the world to delay nonemergent elective surgeries, which results in a large surgery backlog. To develop an operational solution for providing patients timely surgical care with limited health care resources, this study proposes a stochastic control process-based method that helps hospitals make operational recovery plans to clear their surgery backlog and restore surgical activity safely. The elective surgery backlog recovery process is modeled by a general discrete-time queueing network system, which is formulated by a Markov decision process. A scheduling optimization algorithm based on the piecewise decaying ϵ -greedy reinforcement learning algorithm is proposed to make dynamic daily surgery scheduling plans considering newly arrived patients, waiting time and clinical urgency. The proposed method is tested through a set of simulated dataset, and implemented on an elective surgery backlog that built up in one large general hospital in China after the outbreak of COVID-19. The results show that, compared with the current policy, the proposed method can effectively and rapidly clear the surgery backlog caused by a pandemic while ensuring that all patients receive timely surgical care. These results encourage the wider adoption of the proposed method to manage surgery scheduling during all phases of a public health crisis. [ABSTRACT FROM AUTHOR]

Objectives : The aim of this study was to evaluate the clinical outcomes of diode laser as an adjunct to nonsurgical periodontal therapy (NSPT) for residual periodontal pockets in mandibular second molars. Materials and methods : Sixty-seven mandibular second molars (154 residual periodontal pockets) were recruited into the study and randomly assigned to the Laser + NSPT group and the NSPT group. The Laser + NSPT group underwent NSPT adjunct with diode laser radiation (wavelength: 810 nm, power: 1.5 W, 40 s maximum), while the NSPT group underwent nonsurgical periodontal therapy alone. Clinical parameters were measured at baseline (T0) and 4(T1), 12(T2), and 24(T3), weeks after treatment. Results: Periodontal pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP) in both groups showed significant improvements at the end of study compared to baseline. The reductions of PPD, CAL, and BOP in the Laser + NSPT group were significantly greater than NSPT group. At T3, the Laser + NSPT group had a mean PPD of 3.06 ± 0.86 mm, CAL of 2.58 ± 0.94 mm and BOP of 15.49%, while the NSPT group had a mean PPD of 4.46 ± 1.57 mm, CAL of 3.03 ± 1.25 mm and BOP of 64.29%. Conclusions: The diode laser as an adjunct to nonsurgical periodontal therapy may contribute to clinical outcomes for residual periodontal pockets. However, the approach may cause reduction of keratinized tissue width. Trial registration number: This study was registered in the Chinese Clinical Trial Registry ChiCTR2200061194. Clinical relevance: Diode laser as an adjunct to nonsurgical periodontal therapy may contribute to the clinical outcomes for residual periodontal pockets in mandibular second molars. [ABSTRACT FROM AUTHOR]

Purpose: As a member of the C19MC family, miR-526b-5p is mainly expressed in the placental tissue and is a well-known tumor suppressor microRNA. However, its effect on the function of trophoblasts and its role in the development of recurrent spontaneous abortion (RSA) remains unclear. Methods: Transcriptome sequencing, quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, 5-ethynyl-2′-deoxyuridine (Edu) proliferation analysis, cell counting kit-8 (CCK8) assay, Transwell assays, and wound healing were used to detect the proliferation, migration, and invasion capacity of trophoblasts. Target genes of miR-526b-5p were obtained by the dual luciferase reporter system. The promoter-reporter system and ChIP-qPCR were used to prove that c-Myc positively regulated the expression of Foxp1 Results: The miR-526b-5p levels were significantly higher in patients with RSA than in controls. High expression of miR-526b-5p inhibited the proliferation, migration, and invasion of trophoblast cell line. By contrast, low expression of miR-526b-5p promoted the proliferation and migration of trophoblast cell line. Target genes of miR-526b-5p were c-Myc and Foxp1. c-Myc positively regulated the expression of Foxp1 by binding to the Foxp1 promoter location -146/-135. Finally, miR-526b-5p impeded the proliferation, migration, and invasion of trophoblasts by negatively regulating c-Myc by rescue experiments. Conclusion: Thus, miR-526b-5p affected the proliferation, migration, and invasion of trophoblasts by targeting c-Myc and Foxp1. Low expression of c-Myc further deactivated the positive transcriptional regulation of c-Myc on Foxp1, which may be the mechanism of RSA. This study provides potential therapeutic targets and clues for the diagnosis and treatment of RSA. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) conformations of a small molecule profoundly affect its binding to the target of interest, the resulting biological effects, and its disposition in living organisms, but it is challenging to accurately characterize the conformational ensemble experimentally. Here, we proposed an autoregressive torsion angle prediction model Tora3D for molecular 3D conformer generation. Rather than directly predicting the conformations in an end-to-end way, Tora3D predicts a set of torsion angles of rotatable bonds by an interpretable autoregressive method and reconstructs the 3D conformations from them, which keeps structural validity during reconstruction. Another advancement of our method over other conformational generation methods is the ability to use energy to guide the conformation generation. In addition, we propose a new message-passing mechanism that applies the Transformer to the graph to solve the difficulty of remote message passing. Tora3D shows superior performance to prior computational models in the trade-off between accuracy and efficiency, and ensures conformational validity, accuracy, and diversity in an interpretable way. Overall, Tora3D can be used for the quick generation of diverse molecular conformations and 3D-based molecular representation, contributing to a wide range of downstream drug design tasks. [ABSTRACT FROM AUTHOR]

The oxygen-doped porous carbon nitride (O-PCN) was prepared via calcinating oxalic acid and urea to activate peroxydisulfate (PS) for abatement of 17α-ethinylestradiol (EE2) under visible light. The results indicated that O-PCN possessed relatively higher specific area (50.48 m2 g−1), larger pore volume (0.168 cm3 g−1), larger average size (14.33 nm) and thinner layer compared to g-C3N4. This structure feather can utilize light more efficiently because more light can penetrate the pore of O-PCN reflect in the pores and reflect. Most importantly, O-PCN has quasi-full-visible-light response (790 nm) compared to pure g-C3N4 (480 nm), which can broaden utilization efficiency of visible light range. In PS/O-PCN/Vis system, 6 mg/L EE2 can be completely removed only within 20 min, and degradation rate constant of EE2 is 6.81 and 2.00 times than those in PS/g-C3N4/Vis and O-PCN/Vis systems. The h+ and ∙O2− are main contributors for EE2 abatement in the PS/O-PCN/Vis system. The effect of anion (Cl−, HCO3−, NO3− and SO42−) and typical natural organic matters (HA and FA) present in water matrixes on EE2 abatement in this system is explored, and the estrogenic activities of treated process is also evaluated by MCF-7 cell viability. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is one of the most common inherited mental retardation diseases and is caused by the loss of fragile X mental retardation protein (FMRP) expression. The metabotropic glutamate receptor (mGluR) theory of FXS states that enhanced mGluR-dependent long-term depression (LTD) due to FMRP loss is involved in aberrant synaptic plasticity and autistic-like behaviors, but little is known about the underlying molecular mechanism. Here, we found that only hippocampal mGluR-LTD was exaggerated in adolescent Fmr1 KO mice, while N-methyl-D-aspartate receptor (NMDAR)-LTD was intact in mice of all ages. This development-dependent alteration was related to the differential expression of caveolin-1 (Cav1), which is essential for caveolae formation. Knockdown of Cav1 restored the enhanced mGluR-LTD in Fmr1 KO mice. Moreover, hippocampal Cav1 expression in Fmr1 KO mice induced excessive endocytosis of the α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit GluA2. This process relied on mGluR1/5 activation rather than NMDAR. Interference with Cav1 expression reversed these changes. Furthermore, massive cholesterol accumulation contributed to redundant caveolae formation, which provided the platform for mGluR-triggered Cav1 coupling to GluA2. Importantly, injection of the cholesterol scavenger methyl-β-cyclodextrin (Mβ-CD) recovered AMPA receptor trafficking and markedly alleviated hyperactivity, hippocampus-dependent fear memory, and spatial memory defects in Fmr1 KO mice. Together, our findings elucidate the important role of Cav1 in mediating mGluR-LTD enhancement and further inducing AMPA receptor endocytosis and suggest that cholesterol depletion by Mβ-CD during caveolae formation may be a novel and safe strategy to treat FXS. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is characterized by abnormal development of the blood vessels and alveoli in lungs, which largely occurs in premature infants. Exosomes (EXO) from very preterm infants (VPI) with BPD (BPD-EXO) impair angiogenic activities of human umbilical vein endothelial cells (HUVECs) via EXO-miRNAs cargo. This study aimed to determine whether and how BPD-EXO affect the development of BPD in a mouse model. We showed that treating BPD mice with BPD-EXO chronically and irreversibly aggravated lung injury. BPD-EXO up-regulated 139 and down-regulated 735 genes in the mouse lung tissue. These differentially expressed genes were enriched to the MAPK pathway (e.g., Fgf9 and Cacna2d3), which is critical to angiogenesis and vascular remodeling. BPD-EXO suppressed expression of Fgf9 and Cacna2d3 in HUVECs and inhibited migration, tube formation, and increased cell apoptosis in HUVECs. These data demonstrate that BPD-EXO aggravate lung injury in BPD mice and impair lung angiogenesis, plausibly leading to adverse outcomes of VPI with BPD. These data also suggest that BPD-EXO could serve as promising targets for predicting and treating BPD. [ABSTRACT FROM AUTHOR]

Reverse osmosis (RO) is widely used in wastewater reclamation to alleviate the increasingly global water shortage. However, it has an inconvenient defect of biofouling. Some disinfection processes have been reported to select certain undesirable disinfection-residual bacteria (DRB), leading to severe long-term biofouling potential. To provide constructive guidance on biofouling prevention in RO systems, this study performed a 32-day experiment to parallelly compared the biofouling characteristics of RO membranes of DRB after five mature water disinfection methods (NaClO, NH2Cl, ClO2, UV, and O3) and two recently developed water disinfection methods (K2FeO4 and flow-through electrode system). As a result, the DRB biofilm of K2FeO4 and O3 caused a slight normalised flux drop (22.4 ± 2.4% and 23.9 ± 1.7%) of RO membrane compared to the control group (non-disinfected, ~27% normalised flux drop). FES, UV, NaClO and ClO2 caused aggravated membrane flux drop (29.1 ± 0.3%, 33.3 ± 7.8%, 34.6 ± 6.4%, and 35.5 ± 4.0%, respectively). The biofouling behaviour showed no relationship with bacterial concentration or metabolic activity (p > 0.05). The thickness and compactness of the biofilms and the organics/bacterial number ratio in the biofilm, helped explain the difference in the fouling degree between each group. Moreover, microbial community analysis showed that the relative abundance of typical highly EPS-secretory and biofouling-related genera, such as Pseudomonas, Sphingomonas, Acinetobacter, Methylobacterium, Sphingobium, and Ralstonia, were the main reasons for the high EPS secreting ability of the total bacteria, resulting in aggravation of biofouling degree (p < 0.05). All types of disinfection except for NaClO and ClO2 effectively prevented pathogen reproduction in the DRB biofilm. [ABSTRACT FROM AUTHOR]

Evidence for the association between serum copper and zinc status and handgrip strength is very limited only in several observational studies with study participants of specific population or a narrower age range. The aim of this study was to evaluate the association between serum copper, zinc and their ratio and handgrip strength in the general population. This study included adult participants aged 20–80 years with complete data of serum copper and zinc status and handgrip strength from NHANES 2011–2014. Handgrip strength was calculated as the average of the maximum measure obtained in each hand with a grip strength dynamometer and corrected using BMI. Serum copper and zinc levels were measured using inductively coupled plasma dynamic reaction cell mass spectrometry, and their ratios were calculated. The multivariable linear regression and restricted cubic spline models were used. Serum copper level was inversely associated with BMI-corrected handgrip strength, and the beta coefficients (95% confidence intervals) comparing the second, third, and fourth to the lowest quartiles of serum copper level were − 0.17 kg (− 0.26; − 0.08), − 0.22 kg (− 0.32; − 0.13), and − 0.36 kg (− 0.44; − 0.28), respectively (P for trend < 0.001). Non-linear association was detected between serum copper level and BMI-corrected handgrip strength (P < 0.01). Consistent with serum copper, serum copper/zinc ratio was inversely associated with BMI-corrected handgrip strength. However, no significant associations were observed between serum zinc level and BMI-corrected handgrip strength (all P > 0.05). Higher serum copper level and copper/zinc ratios were significantly associated with lower handgrip strength. Further research is needed to address related issues. [ABSTRACT FROM AUTHOR]

Serine synthesis is crucial for tumor growth and survival, but its regulatory mechanism in cancer remains elusive. Here, using integrative metabolomics and transcriptomics analyses, we show a heterogeneity between metabolite and transcript profiles. Specifically, the level of serine in hepatocellular carcinoma (HCC) tissues is increased, whereas the expression of phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in serine biosynthesis pathway, is markedly downregulated. Interestingly, the increased serine level is obtained by enhanced PHGDH catalytic activity due to protein arginine methyltransferase 1 (PRMT1)-mediated methylation of PHGDH at arginine 236. PRMT1-mediated PHGDH methylation and activation potentiates serine synthesis, ameliorates oxidative stress, and promotes HCC growth in vitro and in vivo. Furthermore, PRMT1-mediated PHGDH methylation correlates with PHGDH hyperactivation and serine accumulation in human HCC tissues, and is predictive of poor prognosis of HCC patients. Notably, blocking PHGDH methylation with a TAT-tagged nonmethylated peptide inhibits serine synthesis and restrains HCC growth in an HCC patient-derived xenograft (PDX) model and subcutaneous HCC cell-derived xenograft model. Overall, our findings reveal a regulatory mechanism of PHGDH activity and serine synthesis, and suggest PHGDH methylation as a potential therapeutic vulnerability in HCC. The role of protein arginine methylation in serine metabolism of cancer cells in hepatocellular carcinoma (HCC) remains to be explored. Here, the authors show that phosphoglycerate dehydrogenase (PHGDH) is activated by PRMT1-mediated R236 methylation, promoting serine synthesis, redox homeostasis and HCC growth. [ABSTRACT FROM AUTHOR]

Here, we describe a novel mycovirus, tentatively designated as “Rhizoctonia solani fusarivirus 6” (RsFV6), which was discovered in Rhizoctonia solani AG-3 PT strain 3P-2-2. The virus has a single-stranded positive-sense RNA (+ssRNA) genome of 6141 nucleotides containing two open reading frames (ORFs) and a poly(A) tail. ORF1 encodes a large polypeptide of 1,862 amino acids (aa) with conserved RNA-dependent RNA polymerase (RdRp) and helicase (Hel) domains. ORF2 encodes a putative 167-aa protein of unknown function. BLASTp searches revealed that the ORF1-encoded polypeptide showed the highest sequence similarity (70.67% identity) to that of Rhizoctonia solani fusarivirus 3 (RsFV3), which was isolated from Rhizoctonia solani AG-2-2LP. Multiple sequence alignments and phylogenetic analysis based on RdRp and Hel sequences indicated that RsFV6 could be a novel member of the genus Alphafusarivirus family Fusariviridae. [ABSTRACT FROM AUTHOR]

Fangshan Hanbaiyu is a typical white marble in China that was mainly used in high-grade royal buildings represented by the Forbidden City. Over centuries of natural erosion, most marble artifacts have undergone a variety of deterioration. Based on the deterioration investigation of a total of 726 balusters, 559 dragon heads, and 698 frieze panels around the Hall of Supreme Harmony (Taihe Dian), nondestructive testing technology, including portable x-ray fluorescence, colorimeter, and surface hardness tester, were also used to evaluate the weathering degree and analyze the relationship between the deterioration patterns and the type and spatial distribution of marble components. The results show that the temperature difference stress caused by solar radiation and the erosion caused by rainwater are the main reasons for the weathering. This explains why the components facing the South and East are more deteriorated. In addition, an evaluation method for stone relics deterioration based on three indicators (surface integrity, surface color, and surface hardness) of stone relics was established, and the health index of 12 typical marble components was calculated by this method, the values showed a good linear correlation with the field survey, which can provide a useful reference for subsequent investigation and assessment of the deterioration of the marble relics. [ABSTRACT FROM AUTHOR]

The product service has become one of the key factors to maintain market competitiveness. Therefore, how to balance the service budget and the profits are especially important for enterprises. Besides, the service has catalyzed the upgrading of products, which puts tremendous pressure on both resources and the environment. Therefore, how the government formulates policies to encourage recycling parties to play a vital role in alleviating these problems. This paper establishes Stackelberg game models in three scenarios of manufacturer recycling, retailer recycling, and third-party recycling with service budget constraints; meanwhile, we also explore the impact of service budget and government recycling subsidy on equilibrium results and the selection of recycling strategies. By analysis, when a recycling subsidy is given, the recycling rate in Scenario R under any service budget is always the highest. But the retailer's profit in this scenario only has a weak advantage when the service budget is large enough. For the same social welfare goal, the retailer recycling scenario can achieve the goal the fastest. If recycling subsidy and service budget can be observed, the manufacturer is more willing to entrust recycling activities to the retailer. But the retailer will only participate in recycling activities when the service budget is large enough. Our research can provide decision-making references and scientific support for the retailer, the manufacturer, and the government. [ABSTRACT FROM AUTHOR]

Sexual size dimorphism is widespread in fish species. Although sex growth differences in multiple species have been studied successively, the commonalities of regulatory mechanisms across sexually dimorphic species are unknown. In this study, we performed RNA-seq analysis of four representative fish (loach, half-smooth tongue sole, yellow catfish, and Nile tilapia) with significant growth differences between females and males. Clean reads were identified from four fish species, ranging from 45,718,052 to 57,733,120. Following comparison transcriptome analysis, there were 1,132 and 1,108, 1,290 and 1,102, 4,732 and 4,266, 748 and 192 differentially expressed genes (DEGs) in the brain and muscle of loach, half-smooth tongue sole, yellow catfish, and Nile tilapia, respectively. Furthermore, the expression levels were validated by quantitative real-time PCR (qRT-PCR). Comparative transcriptome profiles of four fish described here will provide fundamental information for further studies on the commonalities of sexually size dimorphic fish in regulating growth differences between females and males. Measurement(s) Transcripts expression profile Technology Type(s) Illumina HiSeq Factor Type(s) sex Sample Characteristic - Organism Misgurnus anguillicaudatus • Cynoglossus semilaevis • Pelteobagrus fulvidraco • Oreochromis niloticus [ABSTRACT FROM AUTHOR]

The nucleotide sequence of a viral double-stranded RNA (dsRNA) from Rhizoctonia solani AG-4 HGIII strain XMC-IF (designated as "Rhizoctonia solani mitovirus 106", RsMV-106) was determined. The complete sequence was 2794 bp in length with a 57.50% A + U content and contained a large open reading frame (ORF) when the fungal mitochondrial genetic code was used. The ORF potentially encodes a 95.76-kDa protein containing a conserved domain of an RNA-dependent RNA polymerase (RdRp). BLASTp analysis revealed that the RdRp domain of RsMV-106 shared 47.52–73.24% sequence identity with those of viruses of the genus Duamitovirus and was most similar (73.24% identity) to that of Alternaria alternata mitovirus 1 (AaMV1). Phylogenetic analysis showed that RsMV-106 is a novel member of the genus Duamitovirus, family Mitoviridae. This is the first report of the full genome sequence of a mitovirus associated with R. solani AG-4 HGIII. [ABSTRACT FROM AUTHOR]

We classify blocks in the BGG category 풪 of modules of non-integral weights for the exceptional Lie superalgebra D(2|1; ζ). We establish various reduction methods, which connect some types of non-integral blocks of D(2|1; ζ) with integral blocks of general linear Lie superalgebras 픤픩(1|1) and 픤픩(2|1). We compute the characters for irreducible D(2|1; ζ)-modules of non-integral weights in 풪. [ABSTRACT FROM AUTHOR]

Enterovirus A71 (EV-A71)–related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings. Hand, foot and mouth disease, caused by enterovirus A71 (EV-A71) infection, is common in children in China. Here, the authors estimate EV-A71 incidence and seroprevalence using data from two longitudinal cohorts and find that, despite high infection rates, a large proportion of children under 6 are susceptible. [ABSTRACT FROM AUTHOR]

In this paper, we prepared a series of Ce1-xTixO2 (x = 0–0.20) nanorods by hydrothermal method, which were used to construct the PdCu/Ce1−xTixO2 catalysts. The Ce1−xTixO2 and PdCu/Ce1−xTixO2 samples were characterized by transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), N2 adsorption–desorption, X-ray diffraction (XRD), inductively coupled plasma optical emission spectrometer (ICP-OES), etc. Catalytic activity, stability, and repeatability of the catalysts for methanol oxidation were investigated. The results show that doping a proper amount of titanium could strengthen the interaction between Ce1−xTixO2 support and PdCu nanoalloy, thus increasing the oxygen vacancy concentration and promoting Pd species with a higher oxidation state. These modified properties are beneficial for the deep oxidation of methanol. The light-off temperature (T50) and full-conversion temperature (T90) of methanol over the PdCu/CeO2 catalyst are 108 °C and 159 °C, respectively. The greatest activity improvement is found for PdCu/Ce0.9Ti0.1O2, which shows the lowest T50 of 88 °C and T90 of 138 °C. Furthermore, neither PdCu/CeO2 nor the modified PdCu/CeO2 catalyst produces by-products and exhibit excellent stability and repeatability throughout the whole test period. This study provides a reference for in-depth understanding and designing of efficient and stable CeO2-based oxidation catalysts. [ABSTRACT FROM AUTHOR]

Water electrolysis is severely impeded by the kinetically sluggish oxygen evolution reaction (OER) due to its inherent multistep four-electron transfer mechanism. However, designing advanced OER electrocatalysts with abundant active sites, robust stability, and low cost remains a huge challenge. Herein, a facile and versatile multiscale manipulating strategy was proposed to construct a novel V-NiFe2O4@Ni2P heterostructure self-supported on Ni foam (V-NiFe2O4@Ni2P/NF). In such unique architecture, the intrinsic OER catalytic activity was greatly boosted by the in-situ generated heterogeneous Ni2P phase induced by precisely selective phosphorylation of the NiFe-precursor, while the synchronous metal V doping stimulated the activity via modulating the electronic configuration, thus synergistically promoting its OER kinetics. In addition, the binder-free catalyst built from three-dimensional (3D) nanosheet arrays (NSs) can offer a large active surface for efficient charge/mass transfer and a robust scaffold for the integrated structure. The as-prepared flexible electrode exhibited superior OER activity with an ultra-low overpotential of 230 mV at 50 mA·cm−2 and outstanding long-term stability for 40 h. This discovery is expected to provide an opportunity to explore efficient and stable commercial materials for scalable, efficient, and robust electrochemical hydrogen (H2) production. [ABSTRACT FROM AUTHOR]

Lepidium meyenii (maca) is an annual or biennial herb from South America that is a member of the genus Lepidium L. in the family Cruciferae. This herb possesses antioxidant and antiapoptotic activities, enhances autophagy functions, prevents cell death, and protects neurons from ischemic damage. Macamide B, an effective active ingredient of maca, exerts a neuroprotective effect on neonatal hypoxic-ischemic brain damage (HIBD), but the mechanism underlying its neuroprotective effect is not yet known. The purpose of this study was to explore the effect of macamide B on HIBD-induced autophagy and apoptosis and its potential neuroprotective mechanism. The modified Rice-Vannucci method was used to induce HIBD in 7-day-old (P7) macamide B- and vehicle-pretreated pups. TTC staining was performed to evaluate the cerebral infarct volume in pups, the brain water content was measured to evaluate the neurological function of pups, neurobehavioural testing was conducted to assess functional recovery after HIBD, TUNEL and FJC staining was performed to detect cellular autophagy and apoptosis, and Western blot analysis was used to detect the levels of proteins in the pro-survival phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway and autophagy and apoptosis-related proteins. Macamide B pretreatment significantly decreases brain damage and improves the recovery of neural function after HIBD. At the same time, macamide B pretreatment activates the PI3K/AKT signaling pathway after HIBD, enhances autophagy, and reduces hypoxic-ischemic (HI)-induced apoptosis. In addition, 3-methyladenine (3-MA), an inhibitor of the PI3K/AKT signaling pathway, significantly inhibits the increase in autophagy levels, aggravates HI-induced apoptosis, and reverses the neuroprotective effect of macamide B on HIBD. Our data indicate that a macamide B pretreatment might regulate autophagy through the PI3K/AKT signaling pathway, thereby reducing HIBD-induced apoptosis and exerting neuroprotective effects on neonatal HIBD. Macamide B may become a new drug for the prevention and treatment of HIBD. [ABSTRACT FROM AUTHOR]

Introduction: This phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. Methods: Patients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity. Results: A total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62–68.20%) and 56.89% for the INF group (95% CI 50.90–62.74%). The difference between the two groups was 5.65% with a 95% CI of – 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable. Conclusions: GB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF. [ABSTRACT FROM AUTHOR]